Cadmium is an environmental and occupational hazard known to cause kidney damage after chronic exposure and to adversely affect the reproductive organs and liver in acute exposure situations. This element, which has known biological function, is accumulated with age and to a greater extent in females than in males. It is retained in liver, kidney and other tissues bound to metallothionein. This proposal is designed toxicity of cadmium. Studies in human materials will examine the relationship between tissue metal and metallothionein levels as affected by age, sex, smoking habit and disease conditions. The significance of urinary metallothionein as a biological indicator of cadmium exposure will be examined in occupationally exposed workers. Studies in resistant and susceptible strains of mice will evaluate the role of sex hormones in hepatic and testicular toxicity of cadmium. The role of sex hormones in hepatic metabolism of cadmium, metallothionein induction and toxicity will be further studied in primary cultures of mouse hepatocytes. Testicular cadmium-binding proteins will be isolated and characterized in an effort to explain the resistance of certain mouse strains to cadmium. With regards to the chronic toxicity of cadmium, the hypothesis that the females may be at greater risk of developing renal dysfunction will be tested in rats. The role of metallothionein-bound cadmium in the etiology of cadmium-induced renal dysfunction will be further examined. It is expected that this research proposal will yield new information that will be of use in understanding some of the risk factors in cadmium toxicity.